Efficacy and Safety of Azilsartan in Participants With Mild to Moderate Uncomplicated Essential Hypertension

A Phase 2, Double-Blind, Randomized, Placebo-Controlled Dose-Ranging Study of the Efficacy, Safety and Tolerability of TAK-536 in Subjects With Mild to Moderate Uncomplicated Essential Hypertension

The purpose of this study was to evaluate the dose-response relationships of azilsartan, once daily (QD) in participants with mild to moderate uncomplicated essential hypertension.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Azilsartan; Drug: Azilsartan; Drug: Azilsartan; Drug: Azilsartan; Drug: Azilsartan; Drug: Candesartan cilexetil

Detailed Description

Hypertension is known to cause multiple organ damage by being combined with not only blood pressure but also other hemodynamics, endocrinological/metabolic abnormalities and genetic factors. This becomes a medically and medical-economically significant problem in Japan The significance of early treatment of hypertension and of long-term control of blood pressure has been increasing year by year.

Takeda Pharmaceutical Company Limited invented TAK-536 (azilsartan), an angiotensin II receptor blocker for decreasing blood pressure. This study investigating the efficacy and safety of azilsartan using candesartan cilexetil, a widely used antihypertensive drug, as a reference control.

• Study Type: Interventional
• Enrollment (Actual): 926
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has mild to moderate uncomplicated essential hypertension.
• Has a sitting diastolic blood pressure between 95 and <110 mmHg and sitting systolic blood pressure between 150 and <180 mmHg at placebo run-in period (Week -2) or randomization visit.

Exclusion Criteria:

• Has a cardiovascular disease or symptoms
• Has been treated with more than 3 different antihypertensives within 27 days prior to placebo run-in period.
• Has a significant hepatic disorder, hyperkalemia, malignant tumor or significant renal impairment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo-matching tablets, orally, once daily for up to 12 weeks.
Experimental: Azilsartan 5 mg QD	Drug: Azilsartan; Azilsartan 5 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 10 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 20 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 40 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 80 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536
Experimental: Azilsartan 10 mg QD	Drug: Azilsartan; Azilsartan 5 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 10 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 20 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 40 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 80 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536
Experimental: Azilsartan 20 mg QD	Drug: Azilsartan; Azilsartan 5 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 10 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 20 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 40 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 80 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536
Experimental: Azilsartan 40 mg QD	Drug: Azilsartan; Azilsartan 5 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 10 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 20 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 40 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 80 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536
Experimental: Azilsartan 80 mg QD	Drug: Azilsartan; Azilsartan 5 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 10 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 20 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 40 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536; Drug: Azilsartan; Azilsartan 80 mg, tablets, orally, once daily for up to 12 weeks.; Other Names: TAK-536
Active Comparator: Candesartan Cilexetil 8 mg titrated to12 mg QD	Drug: Candesartan cilexetil; Candesartan cilexetil 8 mg, tablets, orally, once daily for 4 weeks; titrated to 12 mg, tablets, orally, once daily for up to 8 weeks.; Other Names: Blopress®; TCV-116

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 12).	The change between sitting trough clinic diastolic blood pressure measured at week 12 or final visit from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 12.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 2).	The change between sitting trough clinic diastolic blood pressure measured at week 2 from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 2.
Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 4).	The change between sitting trough clinic diastolic blood pressure measured at week 4 from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 4.
Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 6).	The change between sitting trough clinic diastolic blood pressure measured at week 6 from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 6.
Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 8).	The change between sitting trough clinic diastolic blood pressure measured at week 8 from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 8.
Change from Baseline in Sitting Trough Diastolic Blood Pressure (Week 10).	The change between sitting trough clinic diastolic blood pressure measured at week 10 from diastolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 10.
Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 2).	The change between sitting trough clinic systolic blood pressure measured at week 2 from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 2.
Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 4).	The change between sitting trough clinic systolic blood pressure measured at week 4 from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 4.
Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 6).	The change between sitting trough clinic systolic blood pressure measured at week 6 from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 6.
Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 8).	The change between sitting trough clinic systolic blood pressure measured at week 8 from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 8.
Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 10).	The change between sitting trough clinic systolic blood pressure measured at week 10 from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 10.
Change from Baseline in Sitting Trough Systolic Blood Pressure (Week 12).	The change between sitting trough clinic systolic blood pressure measured at week 12 or final visit from systolic blood pressure measured at baseline. Trough is a time point immediately before the next administration where drug blood concentration is lowest. Mean calculated by using the average (arithmetic mean) of 3 measurements performed at each visit.	Baseline and Week 12.
Number of Participants with a ≥20 mmHg Decrease in Sitting Trough Systolic Blood Pressure and a ≥10 mmHg Decrease in Sitting Trough Diastolic Blood Pressure.	Number of participants designated as responders who have a ≥20 mmHg Decrease in sitting trough systolic blood pressure and a ≥10 mmHg Decrease in sitting trough diastolic blood pressure at week 12 or final visit from baseline.	Baseline and Week 12.
Number of Participants with a Sitting Trough Systolic Blood Pressure of <130 mmHg and a Sitting Trough Diastolic Blood Pressure of <85 mmHg.	Number of participants designated as responders with a sitting trough systolic blood pressure of <130 mmHg and a sitting trough diastolic blood pressure of <85 mmHg at week 12 or final visit from baseline.	Baseline and Week 12.
Incidence of Adverse Events.	Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.	On occurrence (up to Week 12).
Change from Baseline in Supine Systolic Blood Pressure.	The change between supine systolic blood pressure measured at week 12 or final visit from baseline. Supine systolic blood pressure is measured in participants laying on their back in a face-up position once after resting for 2 minutes.	Baseline and Week 12.
Change from Baseline in Supine Diastolic Blood Pressure.	The change between supine diastolic blood pressure measured at week 12 or final visit from baseline. Supine diastolic blood pressure is measured in participants laying on their back in a face-up position once after resting for 2 minutes.	Baseline and Week 12.
Change from Baseline in Standing Systolic Blood Pressure.	The change between standing systolic blood pressure measured at week 12 or final visit from baseline. Standing systolic blood pressure is measured once after participants keep a standing position for 1 minute.	Baseline and Week 12.
Change from Baseline in Standing Diastolic Blood Pressure.	The change between standing diastolic blood pressure measured at week 12 or final visit from baseline. Standing diastolic blood pressure is measured once after participants keep a standing position for 1 minute.	Baseline and Week 12.
Change from Baseline in Sitting Pulse Rate.	The change between sitting pulse rate measured at week 12 or final visit from baseline. Sitting pulse rate is measured at least 3 times in 1- to 2-minute intervals after sitting ≥5 minutes, repeated until 2 consecutive stable measurements are obtained.	Baseline and Week 12.
Change from Baseline in Weight.	The change between weight recorded at week 12 or final visit from baseline.	Baseline and Week 12.
Change from Baseline in Resting 12-lead Electrocardiogram.	The change between electrocardiogram recorded at week 12 or final visit from baseline. Electrocardiogram interpreted using one of the following categories: within normal limits, abnormal but not clinically significant, or abnormal and clinically significant.	Baseline and Week 12.
Number of Participants with a Markedly Abnormal Blood Urea Nitrogen Clinical Laboratory Value.	The number of participants with a markedly abnormal blood urea value nitrogen collected at week 12 or final visit from baseline.	Baseline and Week 12.
Number of Participants with a Markedly Abnormal Uric Acid Clinical Laboratory Value.	The number of participants with a markedly abnormal uric acid value collected at week 12 or final visit from baseline.	Baseline and Week 12.
Number of Participants with a Markedly Abnormal Creatinine Clinical Laboratory Value.	The number of participants with a markedly abnormal creatinine value collected at week 12 or final visit from baseline.	Baseline and Week 12.
Number of Participants with a Markedly Abnormal Creatine Kinase Clinical Laboratory Value.	The number of participants with a markedly abnormal creatine kinase value collected at week 12 or final visit from baseline.	Baseline and Week 12.

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Professor Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: February 1, 2011
• First Submitted That Met QC Criteria: February 1, 2011
• First Posted (Estimate): February 3, 2011

Study Record Updates

• Last Update Posted (Estimate): February 3, 2011
• Last Update Submitted That Met QC Criteria: February 1, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Azilsartan medoxomil; Candesartan; Candesartan cilexetil
• Other Study ID Numbers: TAK-536/CCT-001; U1111-1118-3346 (Registry Identifier: WHO)